ChemPhysMater 1 (2022) 294–309

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ChemPhysMater
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Review Article

Structures, properties, and applications of zwitterionic polymers

Keyu Qu a,#, Zhiang Yuan a,#, Yanyan Wang a, Zhaohui Song a, Xuyang Gong a, Yi Zhao a,
Qiyu Mu a, Qinghong Zhan a, Wenlong Xu a,∗, Linlin Wang b,∗
a
School of Chemistry and Materials Science, Ludong University, Yantai 264025, China
b
State Key Laboratory of Long-Acting and Targeting Drug Delivery System, Shandong Luye Pharmaceutical Co., Ltd., Yantai 264000, China

a r t i c l e i n f o a b s t r a c t

Keywords: Zwitterionic polymers have attracted research attention in recent years owing to their unique molecular struc-
Zwitterionic polymer tures. In the same repeat unit, positive and negative charges are simultaneously located on a pair of cationic and
Structural characteristic anionic groups; therefore, zwitterionic polymers have a large dipole moment and numerous charged groups. Al-
Charged group
though the molecular chain of the zwitterionic polymer can be maintained in an electrically neutral state overall,
Property
the coexistence of the oppositely charged groups confers extremely high polarity and excellent hydrophilicity to
Application
the polymer. At the same time, the electricality of the polymer can be further regulated by the environmental pH
and salt ions, which greatly broadens the scope of applications in different fields. This review introduces various
structures of zwitterionic polymers and analyzes the reasons why zwitterionic polymers exhibit pH responsive-
ness, anti-polyelectrolyte effects, and superior electrical conductivity. The application fields are also summarized
by generalizing the research status of zwitterionic polymers, including applications in antifouling coatings, drug
delivery, wastewater treatment, and sensors, etc.

1. Introduction
In recent years, many advanced polymer materials, including those
used in biomedicine, industrial engineering, and environmental ecol-
ogy, have been developed to meet the needs of sustainable development.
However, the uncontrolled biological pollution generated by common
polymer materials is a significant problem that urgently needs to be
addressed [1–4]. In addition, the low functional group density, unsatis-
factory water-holding capacity, and poor ionic conductivity of polymer
materials limit further development [5–8]. These problems represent
bottlenecks in the development of polymers in various fields. As a re-
sult, polymers that are not only super-hydrophilic but also sufficiently
stable and undergo controllable transitions of the functional groups, and
also exhibit highly sensitive conductivity urgently need to be explored.
Zwitterionic polymers satisfy these requirements and provide a platform
for solving the aforementioned problems.
Zwitterionic polymers have attracted research attention in recent
years owing to their unique molecular structures. In the same repeat
unit, positive and negative charges exist simultaneously; therefore, the
zwitterionic polymer has a high dipole moment and numerous charged
groups, which confers powerful ion conductivity to the polymer [9–11].
Compared with other polymers, although the molecular chain of zwitte-
rionic polymers can be maintained in an electrically neutral state over-
∗
Corresponding authors.
E-mail addresses: xuwenlong@ldu.edu.cn (W. Xu), wanglinlin@luye.com (L. Wang).
#
These two authors contributed equally.
all, the coexistence of the oppositely charged groups leads to extremely
high polarity and excellent hydrophilicity [12–15]. At the same time,
the electricality of the polymer can be further regulated by the environ-
mental pH and salt ions, which greatly broadens the scope of applica-
tions [5,16-19]. Since the 1990s, the earliest zwitterionic material phos-
phorylcholine (PC) has been used on antibacterial surfaces [20]. With
the continuous research and development to advance zwitterionic poly-
mer materials by considering diverse charged groups and other related
chemical groups, different types of zwitterionic structures have contin-
ued to emerge. The successful development of carboxybetaine (CB) and
sulfobetaine (SB) materials for various applications has prompted re-
searchers to understand the principles underlying the functions of zwit-
terionic polymer materials [21–25]. At the same time, the application
of zwitterionic polymers is also expanding in various fields and is grad-
ually being developed by combining other functional chemical groups
to meet the desired characteristics [26–29]. In the field of biomedicine,
antifouling coatings and drug delivery are research hotspots. Zwitteri-
onic polymers have stronger ability to bind water molecules after ionic
solvation [30,31]. This results in a denser hydration layer so that nei-
ther biomolecules nor other types of contaminants can adhere to the
surface of the material. This feature is widely exploited in antifouling
coatings [32]. Zwitterionic polymers possess excellent biocompatibility,
can reduce cytotoxicity, and promote cellular internalization of various
substances [33,34]. Therefore, zwitterionic polymers can be used as vec-
tors for the accurate delivery and effective release of drugs [35–37]. In

https://doi.org/10.1016/j.chphma.2022.04.003
Received 7 March 2022; Received in revised form 13 April 2022; Accepted 13 April 2022
Available online 29 April 2022
2772-5715/© 2022 The Authors. Publishing Services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd. This is an open access article under the CC
BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
K. Qu, Z. Yuan, Y. Wang et al.
Table 1
Common cationic and anionic groups in zwitterionic polymers.
Types of charged groups Structures of charged groups
Cationic
groups amino
Anionic
groups
carboxylate
the field of industrial engineering, owing to the high charge density of
zwitterionic polymers and their propensity for strong electrostatic inter-
actions, it is possible to break the spatial disorder encountered with con-
ventional polymers when zwitterionic polymers are used to remove con-
taminants. Consequently, pollutants with different charges can be effi-
ciently coagulated, forming stable precipitates that can be removed from
wastewater [38–40]. In some emerging fields such as sensors, zwitteri-
onic polymers have been used to prepare hydrogel-type sensors, where
the formed polymer network had a high charge density and abundant
ions, resulting in high conductivity [41,42]. Other studies have shown
that zwitterionic polymers also have broad development potential in
the fields of energy storage devices, actuators, antifreeze, and seawater
desalination [17,43-45].
Herein, we summarize the structural characteristics, properties, and
applications of current zwitterionic polymers. First, we describe the dif-
ferent distributions of charged groups in zwitterionic polymers and some
special properties of zwitterionic polymers themselves. Subsequently,
we summarize the application fields of zwitterionic polymers by gener-
alizing the research status of zwitterionic polymers. In conclusion, the
prospects for developing zwitterionic polymers are discussed.
2. Structural characteristics of zwitterionic polymers
The structural molecular unit in a zwitterionic polymer generally has
a pair of cationic and anionic groups. As shown in Table 1, the cationic
groups include protonated amino [46], quaternary ammonium [37,47-
49], and pyridine [5,50] units, while anionic groups include carboxylate
[24,51], sulfonate [22,27,52,53], and phosphate [26,54,55]. According
to the distribution of charge, zwitterionic polymers can be divided into
two different structures, one has a positive and negative charge on the
same side chain, while in the other, the charges are localized on dif-
ferent side chains. The typical structures of zwitterionic polymers are
summarized in Table 2. There are also a few complex structures that do
not fall neatly into these classifications [6,56,57].
Zwitterionic polymers can be synthesized by copying monomers
containing cationic and anionic functional groups, as shown in
Table 1 [5,24]. The initial synthesis of polymerizable betaine monomers,
followed by copolymerization with other functional monomers is an
achievable approach [54,58]. Grafting zwitterionic functional groups
onto existing polymer long chains is also an option [16,17]. Attraction
and repulsion are two major electrostatic interactions in the structure of
synthetic zwitterionic polymers that can be affected by the pH and salt
ions in the environment. Notably, sulfonic acid betaine-type zwitterionic
polymers have good chemical stability, and their structure and proper-
ties are relatively less pH-sensitive [21,23,53,59]. Through electrostatic
attraction, the zwitterionic polymer chain adopts a folded conformation
that is initially curly and becomes spherical, whereas the zwitterionic
polymer chain expands through electrostatic repulsion [18,19]. These
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ChemPhysMater 1 (2022) 294–309
quaternary ammonium pyridine
sulfonate phosphate
attractive and repulsive interactions also affect the mechanical proper-
ties of zwitterionic polymers [10,60]. At the same time, the structural
characteristics of the rich cationic groups and anionic groups on the
polymer chain impart superior hydrophilicity to the zwitterionic poly-
mer [61–63]. When positive and negative charges are distributed in the
same side chain, the zwitterionic polymer is more hydrophilic because of
the larger density of the cationic and anionic groups, which has a certain
impact on the properties and applications of the polymer [17,22,24,52].
3. Properties of zwitterionic polymers
3.1. pH-responsiveness (isoelectric point phenomenon)
Zwitterionic polymers have been widely used in biomedicine and
industrial engineering to separate proteins [65] and treat industrial
wastewater [24]. The vital mechanism involves selective binding of
the zwitterionic polymers to oppositely charged species through elec-
trostatic interactions. The pH of the environment can easily affect the
electrostatic interactions between zwitterionic polymers and other sub-
stances by shifting the positive and negative charges carried by the
polymer chains. Therefore, zwitterionic polymers are generally pH-
responsive.
Zwitterionic polymers have different zeta potentials in media of dif-
ferent pH. This feature can be used to evaluate the effect of ambient pH
on electrostatic interactions within the polymers. When the zeta poten-
tial is zero, the number of positive and negative charges in the poly-
mer are equal, and the environment of the zwitterionic polymer is at
a certain pH (isoelectric point). At the isoelectric point, the protonated
groups with cationic and anionic charges on the zwitterionic polymer
chain undergo electrostatic attraction. When the pH is higher than the
isoelectric point, the polymer gradually becomes an anionic polyelec-
trolyte. When the pH is lower than the isoelectric point, the polymer
exhibits the properties of a cationic polyelectrolyte. In deviating from
the isoelectric point, as the degree of deviation increases, the groups
on the polymer chain gradually tend to have the same charge, resulting
in electrostatic repulsion (Fig. 1(a)) [66]. Protonation of the groups in
zwitterionic polymers can induce transition of the polymer chains from
negatively to positively charged at pH values below the isoelectric point
[6,66]. The protonation degree (𝛼) is calculated using the Henderson-
Hasselbalch formula [67]:
( )−1
𝛼 = 1 + 10pH−pKa , (1)
where pKa is the acidity constant of the polymer, and represents the
ability of an acid to dissociate hydrogen ions. This shows that 𝛼 is in-
versely proportional to the external pH. With a decrease in the pH of
the environment, the degree of protonation increases, and the groups on
the zwitterionic polymer chain are protonated into cationic species that
can combine with substances carrying anionic charges. As the pH of the
environment increases, the degree of deprotonation increases, and the
K. Qu, Z. Yuan, Y. Wang et al. ChemPhysMater 1 (2022) 294–309

Table 2
Structural characteristics of zwitterionic polymers.

Distribution of positive and negative charge Typical structures of zwitterionic polymers

[16, 37, 46, 64] [17, 24, 46] [5]

[25, 48, 51, 61] [21-23, 52, 53, 59] [26, 54, 55] [5, 47-50] [17]

Note: X = (CH2 )n COO, (CH2 )n CONH, or (CH2 )n S.

Fig. 1. (a) Schematic representation of the charge of zwitterionic polymers at different pH. Figure reproduced with permission from American Chemical Society
[66]. (b) Relative transmittance of zwitterionic polymer solution at different pH. Figure reproduced with permission from American Chemical Society [69]. (c)
pH-responsive swelling of zwitterionic polymer gels. Figure reproduced with permission from American Chemical Society [48].

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K. Qu, Z. Yuan, Y. Wang et al.
groups on the zwitterionic polymer chain are deprotonated into anionic
species, which are prone to binding with cationic species, reflecting the
pH-responsiveness of the zwitterionic polymer [68].
The pH-responsive properties of zwitterionic polymers can lead to
macroscopic phenomena, such as light transmittance and swelling. Zwit-
terionic polymers with the dual properties of thermal response and pH
response can achieve different light transmittances in solutions upon
changing the pH [69]. For example, a zwitterionic polymer designed
by Zhao et al. exhibited upper critical solution temperature (UCST)
behavior in neutral aqueous solutions, resulting in a cloudy solution
and reduced transmittance owing to electrostatic attraction between
the cationic and anionic charges (Fig. 1(b)) [69]. However, as the pH
decreased or increased, the aqueous solution changed from neutral to
strongly acidic or basic; thus, more positive or negative charges might
engage in electrostatic repulsion within the polymer chain, weakening
the electrostatic attraction between the charged groups and reducing the
UCST. Consequently, the solution changed from turbid to transparent.
However, the positive or negative charge introduced into the weakly
acidic or weakly alkaline environment was not sufficient to weaken
the electrostatic attraction; therefore, the light transmittance did not in-
crease significantly. The pH-responsive properties of zwitterionic poly-
mers also affect the gel properties. The pH of the environment affects
the swelling ratio of zwitterionic polymer gels [70]. The swelling ra-
tio of the zwitterionic polymer gel at the isoelectric point is minimized
because of the strong electrostatic interaction between the anionic and
cationic groups on the chain; this interaction attracts and twists the poly-
mer chains together. When the pH deviates from the isoelectric point,
the groups on the polymer chain gradually tend to have the same charge;
thus, the electrostatic attraction between the charges is weakened while
the electrostatic repulsion between charges is enhanced and gradually
dominates, thereby increasing the swelling rate (Fig. 1(c)) [48]. These
features demonstrate the pH-responsiveness of zwitterionic polymers.
One of the key factors affecting the positive and negative charges of
zwitterionic polymers is the pH of the environment. This pH-responsive
property is mainly reflected by the isoelectric point phenomenon and
complexation, which can provide a platform for the controlled release
of substances by changing the structure and composition of the polymer.
3.2. Salt effect
One property of zwitterionic polymers is their special responsive-
ness to salts, which is called the antipolyelectrolyte effect. The addition
of salts to aqueous solutions of zwitterionic polymers increases the sol-
ubility and solution viscosity of such polymers, in sharp contrast to the
polyelectrolyte effect [71].
When a zwitterionic polymer is in a salt-free environment, there
are dipole-dipole interactions and electrostatic interactions between the
zwitterionic polymer chains. Under the influence of these two interac-
tions, the conformation of the zwitterionic polymer collapses [72]. The
conformations of zwitterionic polymers tend to change in salt solutions.
The Debye formula, expressed as follows, can perfectly explain this phe-
nomenon:
[ ]−1∕2
𝑙𝐷 = 4π𝑙𝐵 𝐶𝑆 , (2)
where lB is the Bjerrum length in pure water and CS is the concentra-
tion of added salt. The Debye formula (lD ) represents the range of elec-
trostatic Coulombic interactions, which it is the typical distance over
which two charges sense each other. The salt concentration (CS ) is in-
versely related to the Debye length (lD ) [73]. When the concentration of
the salt solution increases, the Debye length decreases. Meanwhile, the
electrostatic interaction and dipole-dipole interactions in zwitterionic
polymers (intrachain and interchain) are shielded, and the relatively
collapsed cohesive state gradually disintegrates to form a state that is
relatively expanded and dispersed. Therefore, a salt solution is necessary
for the expansion and dispersion of zwitterionic polymers. In addition,
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oppositely charged groups distributed along the side ends of the zwit-
terionic polymer backbone tend to interact with highly polarizable ions
in the salt solution, replacing the dipole-dipole interactions (intrachain
and interchain) and electrostatic interaction of the zwitterionic polymer
[72]. Under this effect, the net charge of the originally neutral zwitteri-
onic polymer chains is no longer zero. The zwitterionic polymer chains
change from a collapsed state to a more open conformational state ow-
ing to electrostatic repulsion between the same charges on the chains.
This phenomenon was theoretically demonstrated by Rajeev et al. using
variational methods [74]. Thus far, researchers have used various char-
acterization methods such as zeta potential analysis [73], viscosity tests
[75], fluorescence correlation spectroscopy [19], and other methods to
analyze the state of zwitterionic polymers in different environments, all
of which have proved the effect of salts on zwitterionic polymers.
The interaction between the zwitterionic polymer chains is highly
dependent on the salt concentration and ionic species [76]. As the salt
concentration increases with the continuous addition of salt, in the ini-
tial stage, the ionic strength of the solution gradually increases, and
the electrostatic attractive interaction and dipole-dipole interactions (in-
trachain and interchain) between the zwitterionic polymer chains are
weakened (Fig. 2(a)) [77,78]. Simultaneously, the extended zwitteri-
onic polymer chain is transformed into a network structure [75]. The
ionic strength is inversely related to the interaction between the zwitteri-
onic polymer chains. For example, scanning electron microscopy (SEM)
observation showed that as the ionic strength increased, the polymer
structure changed from bundle-like (Fig. 2(b)) to a network structure
(Fig. 2(c)) [78]. When the salt concentration increased to a certain value,
the conformation of the zwitterionic polymer reached a stable state.
At this time, the hydrodynamic radius of the zwitterionic polymer no
longer changed [22], which is related to the equilibrium of various in-
teractions in the solution. In terms of the type of salt, the ability of the
cation to affect the interaction of the zwitterionic polymer depends on
the valence of the cation. As the valence of the cation increases, the
interaction between the cation and the zwitterionic polymer increases;
thus, the influence of the cation is proportional to its valence [79]. The
ability of anions to influence the interaction of the zwitterionic polymer
chains is opposite to the typical order of the anion hydration capacity
in the Hofmeister sequence: SO4 2− > CO3 2− > H2 PO4 − > F− > Cl− >
NO3 − > Br− > ClO4 − > SCN− , where the influence of anions is gener-
ally larger than that of cations [80–82]. However, the strongly hydrated
SO4 2− ion in the sequence cannot induce the antipolyelectrolyte effect in
zwitterionic polymers [83]. When SO4 2− is introduced into the zwitteri-
onic polymer solution, the SO4 2− snatches water molecules that interact
with the zwitterionic polymer; therefore, the zwitterionic polymer can-
not be fully dissolved, and this effect may lead to precipitation of the
zwitterionic polymers [22,84]. The macroscopic behavior of zwitteri-
onic polymers in the presence of SO4 2− is in sharp contrast with that in
the presence of other anions. The transmittance of the zwitterionic poly-
mer hydrogel in the SO4 2− environment was found to be significantly
weaker than that in Cl− environment (Fig. 2(d)) [85].
The key factors influencing the antipolyelectrolyte effect of zwitteri-
onic polymers are the concentration and type of salts. This special prop-
erty of zwitterionic polymers enables the design of new smart polymer
surfaces and provides a platform for applications in high-salinity envi-
ronments.
3.3. Conductivity
In recent years, a variety of conductive materials prepared based on
polymer self-conjugated electron conduction have been considered as
very promising candidate materials [86]. However, owing to the rigidity
of the conjugated polymer chain and the accumulation of hydrophobic
fragments, the strength and conductivity of these polymers require fur-
ther improvement [87,88]. Thus, better electron conductivity has been
realized by adding conductive fillers such as metals, MXene [92–95],
carbon nanotubes [96–98], and graphene [99–102] to flexible polymers
K. Qu, Z. Yuan, Y. Wang et al.
Fig. 2. (a) Salt ions disrupt interactions between zwitterionic polymers. (b) (c) SEM images of zwitterionic polymers in salt-free and salt environments. Figure
reproduced with permission from American Chemical Society [78]. (d) Transmittance of zwitterionic polymers in different anionic environments. Figure reproduced
with permission from Elsevier [85].
[89–91] to achieve coordinated toughness and conductivity. However,
most conductive polymer materials prepared based on electron conduc-
tive principles are black because of the addition of opaque metals or
carbon-based films, which limits their practical applications in biomed-
ical fields owing to the visual requirements for conductive materials
[103]. In contrast, ionic conductive polymers are generally transpar-
ent, and zwitterionic polymers are typically ionic conductive polymers
[104,105]. The numerous anionic and cationic groups in the zwitteri-
onic polymer can combine with each other, promoting the separation of
inorganic ions with opposite charges from the polymer chains to form a
large number of free ions. Consequently, the polymers exhibit superior
electrical conductivity [10,11,106]. The high conductivity of the zwit-
terionic polymer makes it a potential gel electrolyte [60] and sensor
material [106].
As the zwitterionic groups increase, the conductivity is enhanced
and the polymer becomes more sensitive to the electric field [9]. Fur-
thermore, zwitterionic polymers can undergo volume shrinkage and ex-
pansion or shape bending responses in an electric field. Both phenomena
are fundamental because of the directional conduction of ions under the
action of an electric field. For the volume response in the electric field,
the electric field not only moves the ions in the solution, but also causes
the free ions of the polymer to undergo directional movement. When a
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ChemPhysMater 1 (2022) 294–309
stable electric current is generated in the zwitterionic polymer, an elec-
tric field is applied to the anion and cation groups, causing the polymer
chain to move, thereby improving the freedom of water [107]. As a re-
sult, water molecules are released from the polymer network, leading
to volume shrinkage. When the electric field is removed, water is reab-
sorbed by the polymer, thereby causing volume expansion. The changes
in the polymer volume also cause a shape-bending response in an elec-
tric field when the zwitterionic polymer is strip-like. When an electric
field is applied, the inorganic ions in the polymer and the free ions in
the solution move along the fixed electric field direction, resulting in
an ion concentration gradient along the direction of the electric field
[108]. Because of the movement of ions to the side adjacent to the an-
ode or cathode, the internal ion distribution in the polymer is uneven,
generating a penetration pressure difference at distinct positions of the
zwitterionic polymer. This is represented as:
∑( )
Δ𝜋 = 𝑅𝑇 𝐶ig − 𝐶og , (3)
where Δ𝜋 is the osmotic pressure increment, R is the Boltzmann con-
stant, T is the absolute temperature, and Cig and Cog are the concentra-
tions of mobile ions inside and outside the zwitterionic polymer, respec-
tively [109]. Through the absorption and release of water, distinct posi-
tions undergo shrinkage or expansion at different levels, thereby causing
K. Qu, Z. Yuan, Y. Wang et al.
the polymer to bend in response to the electric field [110]. As the volt-
age increases, the ions in the solution move faster, thereby generating a
stronger ion concentration gradient, which can increase the bend speed
and angle [111]. These response behaviors can convert electrical en-
ergy into mechanical work; therefore, zwitterionic polymers have good
application prospects in the fields of actuators [17] and drug delivery
systems [58].
4. Applications of zwitterionic polymers
4.1. Antifouling coatings
Antifouling coatings play a key role in the successful application of
artificial materials both in vitro and in vivo [112]. Biological pollution is
currently affecting the development of medical treatment, marine appli-
cations, and other fields, thereby impacting the economy, environment,
and ecology [2,3,113,114]. The introduction of a hydrophilic polymer
coating, such as polyethylene glycol (PEG), on the surface of a mate-
rial is the most common method of preventing biofouling. This type
of polymer forms a dense hydration layer on the surface of the mate-
rial through hydrogen bonding interactions with water, which blocks
contact between biomolecules such as proteins and the surface of the
material, resulting in an amazing antifouling effect [115]. However,
PEG is not suitable for long-term use as the coating will be oxidized
over time, and the antifouling effect will fail owing to the loss of hy-
drophilicity [116,117]. Therefore, a polymer with improved properties
is required to replace PEG. Common features of hydrophilic antifouling
materials are their strong ability to bind water, electroneutrality, and
hydrogen bond acceptors [118]. In a general antifouling environment,
zwitterionic polymers possess all three properties. When the zwitteri-
onic polymer transitions from an acidic to an alkaline environment, the
ratio of positively to negatively charged groups on the zwitterionic poly-
mer chain changes continuously. At the isoelectric point, the numbers of
positively and negatively charged groups are equal, and the net charge
is zero. In this environment, there is no electrostatic interaction between
the antifouling coating and charged pollutants. On moving away from
the isoelectric point, positive and negative net charges reside on the
zwitterionic polymer chain, conferring the properties of cationic and
anionic polyelectrolytes. At this time, the polymer can only exert an-
tifouling activity in an environment with the same electric charge, which
significantly reduces the scope of application [119,120]. The carbonyl
groups of proteins in biomolecules and phospholipids in cells act as hy-
drogen bond acceptors. Zwitterionic polymer chains contain hydrogen
bond acceptor groups such as quaternary ammonium cations, carboxy-
late anions, sulfonate anions, and phosphate ions. Therefore, there are
no hydrogen bonding interactions between the zwitterionic polymers
used in the antifouling field and biomolecules. The electrostatic induc-
tion ability of zwitterionic polymers causes water molecules to interact
strongly with the polymers, forming a denser hydration layer [121].
The existence of this hydration layer prevents pollutants from contact-
ing and adhering to the surface of the material, which acts as a barrier
to pollutants [122]. Grafting of zwitterionic polymers to the surface of
materials is mainly used in the fields of medical antifouling and marine
antifouling.
4.1.1. Biomedical antifouling
The nonspecific adsorption of proteins is considered a major chal-
lenge for many biomedical applications [1,2]. The nonspecific adsorp-
tion of proteins can easily lead to thrombus formation, innate immune
response, and even affect the accuracy of medical devices, resulting in
medical accidents [123]. Zwitterionic polymer antifouling coatings ex-
hibit extremely low protein adsorption. An ultrathin sulfobetaine zwitte-
rionic polymer antifouling membrane-modified glucose sensor reduced
nonspecific adsorption by 99% in an in vitro bovine serum albumin test.
Zwitterionic poly(sulfobetaine acrylamide) grafted onto silicon-rich sil-
icon nitride surfaces exhibited good repellency to fibrin (FIB) solutions
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ChemPhysMater 1 (2022) 294–309
[1,124]. It is more challenging for antifouling coatings to resist multi-
ple protein adsorption in complex media than single protein adsorption
[125]. Yang et al. grafted poly(carboxybetaine acrylamide) onto a gold
surface to create an antifouling coating. This grafted surface achieved
zero protein adsorption in undiluted serum and plasma containing hun-
dreds of proteins [126]. In addition to proteins, cells adhering to the
surface of implanted medical devices can easily cause inflammation and
pain in patients. Cell proliferation makes the implanted medical device
ineffective, and the patient requires further treatment or even a second
operation, which increases the medical cost and burden on the patient
[127,128]. Jin et al. grafted polysulfobetaine and polycarboxybetaine
zwitterionic polymers onto the surface of polyethylene terephthalate
(PET) and used 3T3 cells to test the anti-cell adhesion ability of the sur-
face. 3T3 cells were unable to adhere to the modified surface, suggesting
the potential application of zwitterionic polymer coatings in anti-cell ad-
hesion [129]. Compared to cell adhesion, the consequences of bacterial
adhesion to medical implants are more serious. Postoperative infections
caused by bacteria can lead to implant failure and even death of the im-
plant [130]. Although the hydration layer of the zwitterionic polymer
blocks the adhesion of bacteria, the biocompatibility of the hydration
layer provides a good environment for bacterial growth inside the medi-
cal material. This limits the application of zwitterionic polymers to med-
ical materials. Liu et al. grafted phosphorocholine zwitterionic polymers
onto antibacterial biomedical-grade copolymers, which released NO to
kill bacteria, while the zwitterionic polymer antifouling coating repelled
bacterial adsorption, leading to enhanced antimicrobial efficacy [120].
In another approach, the electrostatic interaction between the positively
charged polymer chains and negatively charged bacteria ruptured the
cell wall of the bacteria and killed the bacteria. Simultaneously, the hy-
dration layer of the zwitterionic polymer exhibited excellent antifouling
ability [129]. Both methods were used to construct an antifouling coat-
ing to repel and kill bacteria by the synergistic effect of the zwitterionic
polymer and other materials.
4.1.2. Marine antifouling
Marine antifouling is a global problem faced by the marine industry.
The undesirable growth of barnacles, diatoms, and green algae forms
large pieces of debris on the underwater surface, reducing product ser-
vice life and causing serious economic losses [3,4]. Modifying zwitteri-
onic polymers on underwater surfaces is a good method of achieving an-
tifouling. For example, polymethacrylate sulfobetaine antifouling coat-
ings grafted onto glass surfaces can inhibit the settlement of green algal
spores and the attachment of diatom cells [131]. However, many re-
ported zwitterionic polymers can modify only one substrate [3,25,132-
134]. Realizing the antifouling effect by modifying the surfaces of vari-
ous substrates with zwitterionic polymers requires an effective strategy.
The catechol groups in dopamines can adhere to most substrate surfaces.
Using dopamine as "bridges" successfully solves the problem of grafting
zwitterionic polymers to substrates. Yeon et al. modified sulfobetaine
zwitterionic polymers on dopamine derivatives and used dopamine ad-
hesion to indirectly graft zwitterionic polymers onto stainless steel, ny-
lon, and titanium dioxide surfaces. These grafted surfaces exhibit excel-
lent antifouling properties [135].
In general, the biocompatibility and low immunological activity of
zwitterionic polymer antifouling coatings make them increasingly pop-
ular in human implant coatings. The stability and excellent antifouling
properties of zwitterionic polymer antifouling coatings make them po-
tential candidates for marine antifouling applications. The antifouling
mechanism of zwitterionic polymer coatings has been confirmed, and
the antifouling effects of various zwitterionic polymers have been fully
studied. As mentioned above, the synergistic effect confers multifunc-
tionality to the zwitterionic polymer antifouling coating and can en-
hance antifouling performance. This may shed light on the next step in
the development of zwitterionic polymers.
K. Qu, Z. Yuan, Y. Wang et al.
4.2. Drug delivery
Drug delivery systems (DDSs) are of great significance in the phar-
maceutical and personal health care industries. DDSs can encapsulate
and carry drugs to therapeutic targets, but current DDSs are often lim-
ited by factors such as poor drug bioavailability, short circulation time,
and uncontrolled drug release [136–138]. The superior properties of
zwitterionic polymers can effectively solve these problems; for exam-
ple, pH-responsiveness enables the controllable release of drugs. Select-
ing zwitterionic polymers as hydrophilic blocks can effectively increase
the circulation time and stability of carriers, enhance cellular internal-
ization, and reduce side effects, et cetera [139]. Taking an anticancer
drug as an example, the drug can usually be delivered through DDSs
such as polymer micelles [47], drug conjugates [140], or nanoparticles
[54] made of zwitterionic polymers.
4.2.1. Polymer micelles
Over the past few decades, many polymeric micelles with unique
core-shell structures have been developed as DDSs [141]. First, self-
assembly of the zwitterionic polymer formed pH-responsive core-shell
micelles under certain conditions, after which the hydrophobic inner
core encapsulated anticancer drugs through hydrophobic interactions,
achieving high-efficiency release of the anticancer drugs under acidic pH
conditions [142]. Zwitterionic polymers are superhydrophilic because of
the presence of abundant ions. Therefore, the hydrophilic shell, as a mi-
cellar structure, can be used to maintain the hydration barrier, prolong
blood circulation time, improve efficacy, and reduce side effects [143].
The DDS of this micellar structure first splits the hydrophobic molecules
in the inner core under weakly acidic conditions and is destroyed, al-
lowing the anticancer drugs in the inner core to be transported into the
outer shell [16]. Subsequently, the surface charge is converted to pos-
itive or negative via reversible protonation through the action of the
zwitterionic polymer (as the outer shell), leading to the same charge
as the drug, which caused the electrostatic repulsion to dominate and
weakened the electrostatic attraction between the charges. Finally, dis-
ruption of the delivery system due to electrostatic repulsion enabled
effective and rapid release of the anticancer substances [144]. There-
fore, micellar delivery systems composed of zwitterionic polymers have
potential applications as anticancer drug carriers in cancer therapy.
4.2.2. Drug conjugates
In addition to micellar structures, conjugates of zwitterionic poly-
mers with therapeutic agents have broad application prospects in the
biomedical field. Compared with general polymers, zwitterionic poly-
mers are more hydrophilic and can exert better protective effects and
improve the solubility of drugs [145]. Drug conjugates constructed with
zwitterionic polymers do not affect the biological activity or protein-
binding affinity of the drugs [146]. Sun et al. constructed a DDS com-
prising zwitterionic polymer-drug conjugates with polylactic acid (PLA)
as the backbone and conjugated them with anticancer drugs using zwit-
terionic polymers (Fig. 3(a)) [140]. Combining the non-degradable zwit-
terionic polymer with the degradable polymer PLA can reduce the side
effects caused by polymer accumulation and the health risks caused by
systemic toxicity, to some extent [147]. The DDS comprising drug con-
jugates had a faster drug release rate in acidic environment because
of the acid-labile bond between the anticancer drug and the polymer
(Fig. 3(b)) [140]. This reflects the application potential of biodegrad-
able zwitterionic polymer-based biomaterials, where zwitterionic poly-
mer drug conjugates are expected to be widely used in biomedical re-
search.
4.2.3. Nanoparticles
Nanoparticles are also promising anticancer DDS, and zwitterionic
polymer-modified nanoparticle DDSs have a longer circulation time and
prevent nonspecific protein adsorption [148]. Therefore, zwitterionic
polymers have been widely used for the construction of nanoparticles.
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The methods of loading drugs into nanoparticle DDSs and the mecha-
nisms of drug release vary. The self-contained hydrophobic segment of
these DDSs could directly enable the loading of anticancer drugs through
hydrophobic interactions, while drug loading in systems without hy-
drophobic segments in the structure can be achieved by grafting onto
the polymer through unstable hydrazone bonds to provide hydrophobic
moieties and drive self-assembly of the nanoparticles [149,150]. Zwit-
terionic polymers lead to nanoparticle drug DDSs through complexa-
tion with metal cations (Fig. 3(c)) [54]. The zwitterion fragments in the
system are protonated in acidic environment and thus have the same
charge as the metal cations in the drug, resulting in electrostatic repul-
sion, which destroys the system structure, resulting in drug release. The
self-polymerized nanoparticles, through the electrostatic attraction of
anions and cations on the polymer, are not conducive to the release of
drugs in the extremely acidic gastric environment, but can promote the
release of drugs in the slightly alkaline intestinal environment. This is
because of the electrostatic attraction between the anions and cations
on the polymer chain in the gastric environment, which results in upper
critical solution temperature behavior. Consequently, the drug-loaded
nanoparticles were more stable and aggregated in the gastric environ-
ment, thereby slowing the release rate of the drug. Conversely, in the
intestinal fluid environment, the pH of the environment in which the
zwitterionic polymer was located changed so that the groups on the
polymer chain gradually tended to have the same charge, weakening
the electrostatic interaction and allowing rapid drug release [5,149].
The nanoparticle DDS constructed by the zwitterionic polymer can ef-
fectively release the loaded drug in intestinal fluid by pH-responsive
stimulation and can prevent the release of drugs in gastric fluid, and
has potential utility as a carrier for oral administration.
This section presents a detailed summary of the use of zwitterionic
polymers to construct various DDSs. The development and application
of zwitterionic polymers have attracted increasing attention due to the
great application potential of these polymers in the field of drug deliv-
ery.
4.3. Wastewater treatment
The existence of dyes, metal ions, and other pollutants in wastewa-
ter not only causes serious damage to the environment, but also threat-
ens human health [6,7]. Consequently, wastewater treatment has be-
come the focus of attention. Zwitterionic polymers are widely used in
water treatment because of their electrostatic interactions with both
positive and negative charges, and their prospective use as adsorbents
[24,63,151], flocculants [152–154], and chelating agents [6,7]. Zwit-
terionic polymers can achieve water purification through chemical or
physical interactions such as coordination bonds, hydrogen bonds, elec-
trostatic adsorption, etc [63,154].
4.3.1. Adsorbents
Factors such as the pH, anion/cation ratio, and solution concentra-
tion have an important impact on the charge density of zwitterionic
polymers and the ionization of adsorbates in the solution, which affects
the water purification ability [24]. When zwitterionic polymers are used
as adsorbents to treat anionic dyes and cationic dyes in aqueous solution,
due to the difference in the charge of the anionic and cationic dyes, the
adsorption of dyes by zwitterionic polymers depends on the nature and
amount of the net charge on the zwitterionic polymers, which can enable
selective adsorption of oppositely charged dyes in the mixture. As the
nature of the net charge on the zwitterionic polymer chain is affected
by changes in the solution pH, the adsorption of anionic and cationic
dyes by the zwitterionic polymer varies with the change in pH [48,155].
Shukla et al. synthesized zwitterionic superabsorbent polymers (SAPs),
which are three-dimensional cross-linked networks that contain anions
and cations. Zwitterionic polymers carry different charges owing to their
protonation and deprotonation in different pH environments, enabling
K. Qu, Z. Yuan, Y. Wang et al.
Fig. 3. (a) Intracellular drug release from zwitterionic polymer drug conjugates. (b) Drug release rates at different pH. Figure reproduced with permission from
Elsevier [140]. (c) Nanoparticles self-assembled from zwitterionic polymers via metal cation chelation. Figure reproduced with permission from American Chemical
Society [54].
them to absorb oppositely charged anionic dyes via electrostatic inter-
actions (Fig. 4(a)) [48]. The deprotonation of zwitterionic polymers in-
creases the number of negatively charged sites and enhances the elec-
trostatic attraction of the zwitterionic polymers to cationic dyes, which
is beneficial for the adsorption of cationic dyes by SAPs, but does not
favor the adsorption of anionic dyes [24,151]. The adsorption capac-
ity of zwitterionic polymers formed by 2-acrylamide-2-methylpropane
sulfonic acid (AMPS) and maleic anhydride (MA) for acid and alkaline
dyes varied with the initial concentration of the dyes in the solution,
which influenced the dye removal rate. The adsorption capacity of the
zwitterionic polymers for dyes gradually tended to balance over time.
In addition to the above effects, the net charge of zwitterionic polymer
chains with different anion and cation ratios and the different charges
on the chains also have a significant effect on the adsorption of anionic
and cationic dyes by zwitterionic polymers (Fig. 4(b)(c)) [24]. Contam-
inants can be dispersed in aqueous solutions in the form of solutes, and
can also form fouling deposits in water, which can be removed owing
to the electrostatic attraction of the zwitterionic polymer to the fouling
deposits. Oppositely charged zwitterionic polymers can adsorb contami-
nants on their surface by electrostatic adsorption to remove surface dirt.
The adsorption of fluorescently labeled proteins was evaluated to sim-
ulate membrane fouling by pollutants, where it was confirmed that the
zwitterionic polymer removed the pollutants deposited in water by elec-
trostatic adsorption, which broadens the scope of application of zwitte-
rionic polymer adsorbents [63].
4.3.2. Flocculants
Zwitterionic polymers can also be used as flocculants to form flocs of
contaminants in solution and remove them from the solution [152,156-
158]. The relationship between the pH of the solution and the pKa of
the polymer affects the polymer morphology. At high pH, polymers are
water-soluble and exist as micelles. Below a critical pH, phase sepa-
ration occurs and the polymers become water-insoluble. Zwitterionic
polymers undergo drastic phase transitions at pH values near the pKa
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[152,155]. The zwitterionic sulfonamide polymer AMPS can separate
hydrocarbon impurities in water. When the solution pH is greater than
the pKa of the sulfonamide present, the polymer is water-soluble and
forms micelles, enabling the isolation of pollutants even at high dilu-
tion. The pH of the solution was reduced by introducing CO2 into the
aqueous solution. When the pH was lower than the critical value, the
polymer became insoluble in water, phase separation occurred, and the
trapped contaminants could be precipitated and removed from the so-
lution. When the supernatant was used for the absorbance test, it was
found that the core region of the micelle was saturated and the mea-
sured absorbance decreased. After flushing with N2 or air, the pH of the
solution returned to the original value. Therefore, AMPS can be reused.
The entire process is illustrated in Fig. 4(d) [152]. In the treatment of
industrial wastewater, the microflocs produced by coagulation are frag-
ile and reversibly formed, and the addition of organic flocculants, such
as zwitterionic polyacrylamide, could improve the stability of the flocs
to obtain larger, denser, and more stable flocs [153]. Within a certain
dose, the total amount of flocculant played a key role in the reaction.
At the initial pH of the wastewater, some acrylic monomers in the poly-
mer were negatively charged because electrostatic interactions made the
flocculation effect more pronounced [156].
4.3.3. Chelating agents
In many industrial fields, the treatment of wastewater containing
heavy or radioactive metal ions is of great importance. However, the
traditional chemical precipitation method has a low removal rate and a
high residual concentration of heavy metal ions, whereas various other
treatment methods such as the oxidation method [159], ion exchange
method [160], and other methods [161] have poor selectivity. The com-
plicated operations and high costs make these methods only suitable for
the small-scale treatment of wastewater [7]. To solve these problems,
the use of zwitterionic polymers as chelating agents to treat wastewa-
ter has become a popular research topic [63,154]. Metal ions can react
with the negatively charged chelating groups in zwitterionic polymers
K. Qu, Z. Yuan, Y. Wang et al. ChemPhysMater 1 (2022) 294–309

Fig. 4. (a) pH-responsive adsorption of anionic and cationic dyes. Figure reproduced with permission from American Chemical Society [48]. (b) Adsorption of
anionic dyes by positively charged zwitterionic polymers. (c) Adsorption of cationic dyes by negatively charged zwitterionic polymers. Figure reproduced with
permission from American Chemical Society [24]. (d) Recovery capacity of the zwitterionic polymer in response to CO2 and pH. Figure reproduced with permission
from American Chemical Society [152].

to neutralize and remove them. Among the existing chemical precipi-
tation methods, the chelation precipitation method has the characteris-
tics of practicality, high efficiency, and low cost, and is especially suit-
able for treating large amounts of heavy metal-containing wastewater.
When a zwitterionic polymer is used as a chelating agent, the negative
charges on the polymer chain can be neutralized by heavy-metal ions,
resulting in twisted and flocculated polymer chains. Polymer chains are
beneficial for bridging the microfloes. The same heavy metal ions can
also react with two or more chelating groups from different polymer
chains, causing small flocs to aggregate and merge into larger flocs,
overcoming the shortcomings of traditional methods [162]. First, the
electronic structure of the metal ion itself affects the chelating effect of
the group attached to the zwitterionic polymer on the metal ion in the
solution. Taking the removal of Cu2+ in an aqueous solution as an exam-
ple, a zwitterionic chelating polymer copolymerized with dimethyl dial-
lyl ammonium chloride and acrylamide monomer was used as a chelat-
ing agent. Owing to the 3d9 electronic structure of Cu2+ , coordination
compounds tended to be formed in the removal of Cu2+ [7]. Second,
the structure of the metal ions and the pH of the external environment
both affect chelation. Radioactive metal ions will pollute the environ-
ment and cause serious harm to humans. Using Sr2+ as an example, a
zwitterionic polymer synthesized from N-vinylimidazole was used as a
chelating agent to remove Sr2+ . The polymer adsorbed Sr2+ through sul-
fonate and carboxylate groups in the repeating units. With a change in
pH, the adsorption capacity of the chelating agent also changed. At pH
= 3, H+ and Sr2+ at higher concentrations in the solution competed for

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sulfonate and carboxylate, causing chelation of the metal ions by the
zwitterionic polymer to decrease, and the chelating ability of the zwit-
terionic polymers for metal ions was weakened, resulting in a decrease
in the adsorption capacity of the polymer [6]. Therefore, when using
zwitterionic polymers to remove metal ions, attention should be paid
to the pH of the environment to ensure that the zwitterionic polymers
can exert their excellent chelating ability and achieve the desired water
purification effect.
Overall, zwitterionic polymers are widely used in wastewater treat-
ment owing to their excellent properties, where the water purification
effects are achieved through the formation of coordination bonds, hy-
drogen bonds, electrostatic adsorption, etc.
4.4. Sensor
Most research on zwitterionic polymers for sensor applications has
focused on zwitterionic hydrogels. Zwitterionic hydrogels are soft ma-
terials with densely distributed three-dimensional network structures
comprising cations and anions [41]. In recent years, the applications of
zwitterionic hydrogel sensors have mainly focused on wearable stress-
strain sensors and environmental response sensors.
4.4.1. Wearable stress-strain sensors
Appropriate electrochemical and mechanical properties are critical
for employing hydrogels as stress-strain sensors, where these properties
are strongly related to the polymer network composition. Traditional
sensors are primarily based on polyacrylamide and polyvinyl alcohol.
The limited electrochemical and mechanical properties of these com-
pounds greatly restricts their development in the field of wearable stress-
strain sensors [163,164]. Compared to these hydrogels, zwitterionic hy-
drogels have unique advantages. In a polymer network constructed by
zwitterionic chains, the zwitterionic groups can accelerate the separa-
tion of ions during ion migration, resulting in higher ionic conductivity
[165]. When a zwitterionic hydrogel is subjected to an external force
or deformation, the size of the ion channels in the zwitterionic poly-
mer network changes, which affects the ion transport rate. Finally, the
resistance of the zwitterionic hydrogel changes, resulting in a series of
related electrical signal changes [10]. For example, as the degree of de-
formation of the zwitterionic hydrogel gradually increased, the resis-
tance of the hydrogel also increased gradually. The large gauge factor
(GF) of zwitterionic polymers is advantageous for their application in
wearable stress-strain sensors [166]. Zwitterionic hydrogels exhibit re-
markable sensitivity to pressure. When mild, moderate, or severe forces
were applied to a zwitterionic hydrogel sensor, the reflected resistance
values were significantly different [10]. Hydrogen bonding and dipole-
dipole interactions between a zwitterionic hydrogel and human skin en-
abled the zwitterionic hydrogel to fit seamlessly onto the skin. There-
fore, zwitterionic hydrogels can accurately sense various changes and
magnify electrical signals [167]. Dipole-dipole interactions and electro-
static interactions in zwitterionic hydrogels cause cross-linking between
the zwitterionic chains, forming a dynamic cross-linked network. Under
the influence of these interactions, zwitterionic hydrogels exhibit ex-
cellent self-healing, recoverablity, and energy-dissipative abilities, en-
abling them to resist large deformations without being destroyed [168].
Zwitterionic polymers can be easily modified, allowing the development
of monomers with desirable structures. Zwitterionic hydrogels synthe-
sized from such monomers exhibit high tensile strengths [169]. Based
on these characteristics, zwitterionic hydrogels are widely used in hu-
man motion detection, heartbeat and pulse detection, and other fields.
When a zwitterionic hydrogel was attached to each joint of the human
body, it responded to various human actions with different electrical
signals. By processing and analyzing the electrical signals, an athlete’s
exercise habits can be inferred, which is helpful in detecting whether
the exercise action is standard [166]. When the zwitterionic hydrogel
was attached to the throat of the human body, it could also respond
to different electrical signals generated by diverse pronunciations, such
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ChemPhysMater 1 (2022) 294–309
as “Hi” and “Chinese” (Fig. 5(a)(b)), etc. By processing these electri-
cal signals, the words spoken can be inferred [10]. A zwitterionic hy-
drogel was attached to the arterial pulse of the human wrist, and the
electrical signal was transmitted from the signal-monitoring panel to a
personal computer through a wireless Bluetooth device. The electrical
signal processed by the personal computer accurately reflected the beat
of the human heart (including clearly separated P waves, QRS waves,
and T peaks), indicating that the sensor can detect heartbeat (Fig. 5(c))
[170].
4.4.2. Environmental response sensors
Zwitterionic hydrogels with good electrical conductivities and me-
chanical properties can accurately convert changes in the external en-
vironment (temperature, humidity, etc.) into electrical signals with ex-
cellent reversibility and repeatability. In terms of temperature sensors,
the temperature-dependence of the electrostatic interactions between
cationic and anionic groups enables the visual detection of tempera-
ture changes by zwitterionic hydrogels. The hydration states of the poly-
mer chains differed at different temperatures. The zwitterionic polymer
chains were surrounded by water molecules, and the larger or more
hydrophobic groups interacted to reduce the binding capacity of the
water molecules. Finally, the zwitterionic polymer precipitates resulted
in phase separation (opaqueness). This interaction is interrupted as the
temperature increases, making the zwitterionic hydrogel transparent
[171]. For example, the dopamine-triggered zwitterionic hydrogel pre-
pared by Zhang et al. exhibited a reversible transparent-opaque transi-
tion with changes in temperature (Fig. 5(d)) [172]. Simultaneously, the
change in structure caused a change in the ion mobility, which changed
the electrical signal of the zwitterionic hydrogel [173]. As another ex-
ample, Liu et al. designed a wearable heat-detection sensor using zwitte-
rionic hydrogels. When the human body was at a normal temperature of
36 ◦ C, the resistance of the sensor was 106 Ω. When the temperature of
the human body reached 40 ◦ C, the resistance of the sensor was 103 Ω.
From the change in the resistance, it can be concluded that the wearable
heat-detection sensor has very high resolution for the temperature of the
human body [166]. In terms of humidity sensors, zwitterionic hydrogel-
based humidity sensors are more sensitive for the detection of humidity.
There is strong interaction between the zwitterionic network and water
molecules [169]. The water molecules adsorbed by hygroscopic zwitte-
rions increase the free volume of the polymer chains, weaken the ionic
interactions, and enhance the ion mobility. Therefore, the zwitterionic
hydrogel humidity sensor offers more sensitive detection [174]. Based
on this principle, the zwitterionic polymer humidity sensor designed by
Li et al. exhibited typical synaptic behavior, such as paired pulse facili-
tation. This enabled the sensor to learn and forget features, with tunable
memory, thus giving the sensor artificial intelligence and enabling the
location of water sources [175].
Zwitterionic polymer hydrogels have been extensively studied
for various sensor applications owing to their superior electrical
conductivity, excellent mechanical properties, and sensitive stimuli-
responsiveness. Zwitterionic hydrogels have great potential for use
in next-generation high-performance smart biochemical sensors. At
present, research on such sensors is still in its infancy, and many issues
need to be further explored.
4.5. Other applications
In addition to these applications, zwitterionic polymers have a wide
range of applications in energy storage devices, actuators, antifreeze,
and seawater desalination.
4.5.1. Energy storage devices
The low volatility and temperature-resistance of polymer electrolytes
have led to a wide range of applications in energy storage devices
[176,177]. The ultra-strong ionic conductivity and wide electrochemi-
K. Qu, Z. Yuan, Y. Wang et al.
Fig. 5. (a)(b) Electrical signals generated by different pronunciations. Figure reproduced with permission from American Chemical Society [10]. (c) Electrical signals
detected using zwitterionic polymer hydrogel sensors. Figure reproduced with permission from American Chemical Society [170]. (d) Transparent-opaque transition
of zwitterionic hydrogels with changing temperature. Figure reproduced with permission from American Chemical Society [172].
cal window of zwitterionic polymers in polymer electrolytes are research
hotspots.
The ion transport rate is an important factor in determining the prop-
erties of energy storage devices. Zwitterionic polymer electrolytes pro-
vide a physical framework for ion transport. Under the action of an ex-
ternal electric field, the counter ions on the zwitterionic chain are eas-
ily separated, and the ions can easily migrate to the surface of the elec-
trode along the migration channel, which reduces energy loss during the
ion migration process. Therefore, the ion transport rate in energy stor-
age devices has been significantly improved [178]. Excellent reusability
is critical for extending the life of energy storage devices. Zwitterionic
polymers are compatible with the anode interface and can form a sta-
ble solid electrolyte interface (SEI). The SEI layer provides more nucle-
ation sites and adjusts the distribution of charges, which promotes the
uniform distribution of metal cations and prevents the nucleation and
growth of metal dendrites. This in turn improves the reusability of the
energy storage device. For example, under the influence of the SEI, no
sudden voltage fluctuations were observed in multiple charge-discharge
cycle tests. In multiple resistance impedance tests, the resistance did not
change [179,180].
Zwitterionic polymers are not only used in electrolytes, but have
also been studied for modifying electrode materials. Lu et al. modified
electrode materials using polysulfobetaine-based zwitterionic polymers.
The three-dimensional structure of the zwitterionic polymer gel allevi-
ated the agglomeration of particles on the electrode surface, increased
the mesoporosity, and shortened the conduction path of Na+ during the
charging and discharging processes, thereby improving the electrical
conductivity of the material [181].
Zwitterionic polymers are promising electrolyte components and
electrode modifiers. Zwitterionic polymers have great potential and re-
search value in the field of energy storage devices.
4.5.2. Actuators
Recently, many polymers capable of responding to environmental
changes have been developed as hydrogel actuators. Examples include
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thermally responsive actuators such as poly(N-isopropylacrylamide)
combined with other materials, pH-responsive actuators such as chi-
tosan/carboxymethyl cellulose, and other actuators [108,182-184].
Zwitterionic actuators are predominantly heterogeneous. Compared
to heterogeneous-structured hydrogels, homogeneous-structured hydro-
gels are typically isotropic materials, where expansion and contrac-
tion of the gels generally cause slow shape/volume deformation un-
der the stimulation of various environmental changes. The presence
of two heterogeneous layers induces different or diametrically opposed
volume/shape changes that amplify the local stress between the two
layers. Therefore, the shape of the heterogeneous hydrogel can change
rapidly, meeting the requirement for fast braking of the hydrogel actu-
ator [185,186]. Zwitterionic polymers are sensitive to salts, and many
types of zwitterionic salt-responsive actuators have been developed to
address the lack of salt-responsive actuators. Bilayer heterogeneous
zwitterionic hydrogels can exhibit shape changes during swelling and
shrinking in different environments. In a salt environment, the degree
of bending of bilayer heterogeneous zwitterionic hydrogels is affected
by the concentration and type of salt. When the concentration of the salt
solution was increased gradually, the bilayer heterogeneous zwitterionic
hydrogels gradually adopted a curled conformation. When placed in an
aqueous environment, the bilayer heterogeneous zwitterionic hydrogels
rapidly curled in the opposite direction. Anions played a major role in
the deformation of the bilayer heterogeneous zwitterionic hydrogels.
The bending direction of the bilayer heterogeneous zwitterionic hydro-
gel in the presence of hydrophobic anions was opposite to that in the
presence of hydrophilic anions [44]. For example, Xiao et al. designed
a bilayer heterogeneous zwitterionic hydrogel composed of polycations
and polyzwitterions, and used the hydrogel to fabricate an eight-arm
gripper. In a salt environment, the gripper bent downward; when trans-
ferred to an aqueous environment, the gripper bent upward. The entire
process completed the capture, transmission, and release of an object,
as shown in (Fig. 6) [28].
The effect of salts on zwitterionic polymers is key to the shape
change of zwitterionic hydrogels. Heterogeneous zwitterionic hydrogel
K. Qu, Z. Yuan, Y. Wang et al.
Fig. 6. Entire process of grasping and releasing objects by the eight-arm gripper.
Figure reproduced with permission from American Chemical Society [28].
salt-responsive actuators enrich the applications of soft actuators and
have unlimited development potential.
4.5.3. Antifreeze
The excellent hydration properties of zwitterionic polymers make
them promising candidates for antifreeze coatings. For example, an-
tifreeze coatings with excellent antifreeze properties were developed
from dopamine and zwitterionic polymers. These coatings can tightly at-
tract water molecules through electrostatic interaction with the charges
on the zwitterionic polymer chains, thereby trapping water molecules
and forming ice water [14]. The relaxation time of a water molecule can
reflect the combined state of the zwitterionic polymer chains and water
molecules [17]. The relaxation time of a water molecule in the vicinity
of a zwitterionic polymer chain was longer than that of water in the pres-
ence of other polymers. This indicates that polymer chains containing a
large number of anion and cation groups can stabilize the oscillation of
water molecules, which slows the freezing process [13,14,29]. There-
fore, the stronger the hydration ability of the antifreeze coating, the
better is its antifreeze performance. Wang et al. also used zwitterionic
polymers to prepare coatings with antifog and antifreeze capabilities.
The coating exhibited good antifog and antifreeze properties, even un-
der severe fogging and frosting conditions. The coating uniformly dis-
persed the adsorbed water molecules to prevent the formation of fog and
frost through hydrogen bonding interactions between the zwitterionic
polymers [29].
Antifreeze agents are currently widely used to prevent the freezing of
hydrogels at sub-zero temperatures because most conventional hydro-
gels lose their properties at low temperatures, which limits their wide
application [187,188]. Zwitterionic polymers can be used to synthesize
gels with antifreeze properties that can be prepared as multimodal ar-
tificial skins for soft robotic applications. A zwitterionic polymer en-
dowed the gel with good low-temperature freezing resistance, enabling
the ionic device to operate even at low temperatures. Combining this
multimodal artificial skin with a soft robotic gripper made it suitable
for applications in various environments [17]. A study by England et al.
showed that a zwitterionic polymer gel could retain as high as 30% wa-
ter in the non-freezing state at −20 ◦ C [45].
4.5.4. Desalination
Research on zwitterionic polymers for desalination has primarily fo-
cused on zwitterionic hydrogels. Owing to the densely distributed an-
ionic and cationic charged groups, the zwitterionic hydrogel can inter-
act with both salt ions and water molecules, making the zwitterionic
hydrogels salt-tolerant and conferring strong hydration capacity to the
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hydrogels, laying the foundation for exploiting the unique advantages
of zwitterionic hydrogels in solar desalination [189–191].
The world faces severe freshwater shortages, where desalination is
considered the most promising solution to this problem [192]. Many
technologies have been developed for extracting fresh water from sea-
water, among which solar steam technology for efficient seawater de-
salination has attracted public attention [193]. The key to solar desalina-
tion is developing advanced materials that accelerate solar water evap-
oration. However, current photothermal materials generally have the
problem of insufficient interaction with water and ions, which slows
desalination in solar seawater desalination systems when the salt con-
centration increases, and the crystallization of solid salt blocks the steam
channel, which limits the application of these systems to actual seawa-
ter [194,195]. Zwitterionic hydrogels, as photothermal materials, have
functions such as good water absorption capacity, inherent photother-
mal conversion performance, and electrostatic repulsion; thus, the de-
velopment of photothermal zwitterionic hydrogels into evaporators has
become a research hotspot [196]. For example, a solar steam generator
based on hierarchical porous zwitterionic hydrogels achieved excellent
desalination of seawater, driven by sunlight. This zwitterionic hydro-
gel can rapidly absorb water through capillary forces because of its hy-
drophilic hydrogel network and hierarchical porous channels, enabling
rapid water replenishment during seawater desalination. The zwitteri-
onic groups in the zwitterionic hydrogel can capture oppositely charged
substances in seawater through the strong interaction between the zwit-
terionic hydrogel and water and ions. All of these features enhanced
the hydration performance of the solar steam generator in different salt
water systems. The system showed good salt tolerance and was used to
produce fresh water quickly and stably [197]. Because biodegradable
natural biomass materials have the advantages of being cheap and low-
density, they have been composited with zwitterionic hydrogel coatings
to make solar seawater desalination devices having unique honeycomb
porous structures with low density and low thermal conductivity. The
pressure difference created by the capillary force of this structure makes
it an efficient water-delivery system. The zwitterionic groups on the
zwitterionic hydrogel segments can not only endow natural biomass ma-
terials with the ability to resist salt precipitation, but also endow them
with excellent anti-biofouling properties. Because of the electrostatic ef-
fect of the zwitterionic hydrogel and the porous structure of the natural
biomass material, the salt can diffuse downward, which gives the evap-
orator excellent salt tolerance. The charged groups on the zwitterionic
polymer chain have strong ability to bind water molecules, which builds
a dense hydration layer that prevents damage to the evaporation device
caused by microorganisms in the ocean [43].
5. Conclusion
Zwitterionic polymers have been widely used in various applications.
The existence of positive and negative charges in the same repeating
unit is a key factor in the wide application of zwitterionic polymers.
This review describes the various structures of zwitterionic polymers,
and the relationship between the structural characteristics and proper-
ties. The origins of the pH-responsiveness, anti-polyelectrolyte effect,
and superior electrical conductivity of zwitterionic polymers were ana-
lyzed. Materials synthesized from zwitterionic polymers are hydrophilic,
biocompatible, and environmentally responsive, enabling their wide use
in the fields of biomedicine and industrial engineering. With the contin-
uous expansion of applications, problems with zwitterionic polymers
have been exposed. The current structure of zwitterionic polymers can-
not meet the requirements for further development, and more zwitte-
rionic polymers with new-type ideal structures need to be synthesized.
Many studies on zwitterionic polymers lack implementation in real en-
vironments; therefore, great effort is needed in the next stage of devel-
opment to solve this problem. Although the development of zwitterionic
polymers still faces many serious challenges, materials synthesized from
zwitterionic polymers are considered to be of high quality. In recent
K. Qu, Z. Yuan, Y. Wang et al.
years, zwitterionic polymers have been gradually expanded into some
emerging fields, and they have immeasurable development potential in
fields that require improvement, such as medicine, biosensors, energy
storage devices, and seawater desalination. This review covers the re-
cent research progress on zwitterionic polymers, provides some inspir-
ing design examples, highlights existing problems in the development of
zwitterionic polymers, and suggests prospects for future development.
This review may lay the foundation for the next step in the development
of zwitterionic polymers.
Declaration of Competing Interest
The authors declare no conflict of interest.
Acknowledgments
This study was financially supported by the National Natural Science
Foundation of China (No. 22102067).
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